The common HLA class I-restricted tumor-infiltrating T cell response in HPV16-induced cancer
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Published:2022-12-16
Issue:
Volume:
Page:
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ISSN:0340-7004
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Container-title:Cancer Immunology, Immunotherapy
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language:en
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Short-container-title:Cancer Immunol Immunother
Author:
Santegoets Saskia J.,Welters Marij J. P.,Schrikkema Deborah S.,Freriks Manon R.,Kok Hanna,Weissbrich Bianca,van den Branden Anouk,Linnemann Carsten,Schumacher Ton N.,Adhikary Sabina,Bendle Gavin,van der Burg Sjoerd H.
Abstract
AbstractImmunotherapies targeting truly tumor-specific targets focus on the expansion and activation of T cells against neoantigens or oncogenic viruses. One target is the human papilloma virus type 16 (HPV16), responsible for several anogenital cancers and oropharyngeal carcinomas. Spontaneous and vaccine-induced HPV-specific T cells have been associated with better clinical outcome. However, the epitopes and restriction elements to which these T cells respond remained elusive. To identify CD8+ T cell epitopes in cultures of tumor infiltrating lymphocytes, we here used multimers and/or a functional screening platform exploiting single HLA class I allele-engineered antigen presenting cells. This resulted in the detection of 20 CD8+ T cell responses to 11 different endogenously processed HLA-peptide combinations within 12 HPV16-induced tumors. Specific HLA-peptide combinations dominated the response in patients expressing these HLA alleles. T cell receptors (TCRs) reactive to seven different HLA class I-restricted peptides could be isolated and analysis revealed tumor reactivity for five of the six TCRs analyzed. The tumor reactive TCRs to these dominant HLA class I peptide combinations can potentially be used to engineer tumor-specific T cells for adoptive cell transfer approaches to treat HPV16-induced cancers.
Funder
Oncode base fund to SHvdB
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Immunology,Immunology and Allergy
Reference46 articles.
1. Forman D, de Martel C, Lacey CJ, Soerjomataram I, Lortet-Tieulent J, Bruni L, Vignat J, Ferlay J, Bray F, Plummer M, Franceschi S (2012) Global burden of human papillomavirus and related diseases. Vaccine 30(Suppl 5):F12-23. https://doi.org/10.1016/j.vaccine.2012.07.055 2. Serrano B, de Sanjosé S, Tous S, Quiros B, Muñoz N, Bosch X, Alemany L (2015) Human papillomavirus genotype attribution for HPVs 6, 11, 16, 18, 31, 33, 45, 52 and 58 in female anogenital lesions. Eur J Cancer 51:1732–1741. https://doi.org/10.1016/j.ejca.2015.06.001 3. Castellsagué X, Alemany L, Quer M, Halec G, Quirós B, Tous S, Clavero O, Alòs L, Biegner T, Szafarowski T, Alejo M, Holzinger D, Cadena E, Claros E, Hall G, Laco J, Poljak M, Benevolo M, Kasamatsu E, Mehanna H, Ndiaye C, Guimerà N, Lloveras B, León X, Ruiz-Cabezas JC, Alvarado-Cabrero I, Kang CS, Oh JK, Garcia-Rojo M, Iljazovic E, Ajayi OF, Duarte F, Nessa A, Tinoco L, Duran-Padilla MA, Pirog EC, Viarheichyk H, Morales H, Costes V, Félix A, Germar MJ, Mena M, Ruacan A, Jain A, Mehrotra R, Goodman MT, Lombardi LE, Ferrera A, Malami S, Albanesi EI, Dabed P, Molina C, López-Revilla R, Mandys V, González ME, Velasco J, Bravo IG, Quint W, Pawlita M, Muñoz N, de Sanjosé S, Xavier Bosch F (2016) HPV involvement in head and neck cancers: comprehensive assessment of biomarkers in 3680 patients. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djv403 4. Piersma SJ, Welters MJ, van der Hulst JM, Kloth JN, Kwappenberg KM, Trimbos BJ, Melief CJ, Hellebrekers BW, Fleuren GJ, Kenter GG, Offringa R, van der Burg SH (2008) Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element. Int J Cancer 122:486–494. https://doi.org/10.1002/ijc.23162 5. Welters MJP, Ma W, Santegoets S, Goedemans R, Ehsan I, Jordanova ES, van Ham VJ, van Unen V, Koning F, van Egmond SI, Charoentong P, Trajanoski Z, van der Velden LA, van der Burg SH (2018) Intratumoral HPV16-specific T cells constitute a type I-oriented tumor microenvironment to improve survival in HPV16-driven oropharyngeal cancer. Clin Cancer Res 24:634–647. https://doi.org/10.1158/1078-0432.CCR-17-2140
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